Ketamine-Induced Urologic Insult (KIUI)

Abstract

K etamine initially introduced as an anesthetic agent in the 1960s, is a receptor complex antagonist n-methyl-d-aspartic acid that has been used as an anesthetic and/or analgesic for many years. In the past decade the use of ketamine as an analgesic or "analgesic adjuvant" appears to have increased. Subanesthetic doses of ketamine have been utilized for analgesia and opioid-sparing effects in chronic pain as well as in refractory cancer pain, and palliative medicine (1-11). Additionally, recently its use studied seems to have grown for chronic noncancer pain (12,13). Its increased use studied overall has largely been for neuropathic pain and especially for the treatment of refractory complex regional pain syndrome (14-17). Ketamine has also been studied to reduce allodynia in patients with complex regional pain syndrome (18). Different routes of administration have been reported to produce beneficial results such as low-dose intranasal (S)-ketamine in patients with complex regional pain syndrome (18). The mechanism of action has been considered to be mainly a noncompetitive antagonism of the N-methyl-D-aspartic acid (NMDA) receptor [19], however, its mechanisms of action may be extremely complex as ketamine may interact with multiple other receptors (19,20). Ketamine has also been shown to inhibit tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) gene expressions in lipopolysaccharide (LPS)-activated macrophages (21). It has even been speculated that the antiproinflammatory effects may be responsible for antihyperalgesic effects of ketamine (22). The ketamine molecule contains a chiral carbon atom marking a chiral center. Ketamine can exist in two forms, or enantiomers; S-ketamine and R-ketamine. The physical properties of the enantiomers are identical, but their interactions with complex molecules, underlying PK/PD parameters, might differ (23). The elimination clearance of S-ketamine is more than that of R-ketamine (24). Although anesthesiologists and pain specialists alike are familiar with the classic and common potential adverse effects of ketamine, they may not be as familiar with an increasingly recognized potential association of ketamine that clinicians should be aware of when prescribing ketamine. The observation that ketamine may lead to significant urological side-effects was first recognized in chronic ketamine recreational use (25-27). In the South West of England, Cottrell and colleagues have reported increasing numbers of patients referred to urological services with complications of chronic ketamine use (28). Other cases have been reported in mainland Europe, Canada, Malaysia (26, 29) and the UK (30). Chen and colleagues discovered 4 female patients, ages 18 to 25 years, who presented to emergency department (ED) with urinary urgency, frequency, and pelvic pain, who had negative work-up and no response to antibiotic therapy were diagnosed with presumed interstial cystitis (31). More detailed history revealed that they were recreational ketamine users. Their symptoms significantly i...

Pathophysiology, clinical presentation, and management of ketamine-induced cystitis

“…The dysregulation of purinergic neurotransmission may underlie the detrusor overactivity in this animal model [ 18 ]. A denuded epithelium, chronic inflammation, ulcerative cystitis, and erythematous necrotic cystitis are frequently found in ketamine cystitis bladders [ 19 ]. Another study reported that ketamine enhanced the generation of oxidative stress mediated by mitochondria- and endothelial reticulum-dependent pathways.…”

The role of ketamine in the treatment of treatment-resistant bipolar depression

“…Η κεταμίνη είναι ουροτοξική (επαγόμενη από κεταμίνη ουροτοξικότητα (Ketamine-induced urological toxicity, KIUT) σε περιπτώσεις βαριάς χρήσης κεταμίνης κι ένα ποσοστό 20-30% των ατόμων που κάνουν συχνή χρήση της αναφέρει αιτιάσεις σχετιζόμενες με την ουροδόχο κύστη. 26,46 Η κατάχρηση λοιπόν της κεταμίνης κι όχι η χορήγησή της σε θεραπευτικό πλαίσιο προκαλεί τοξικά αποτελέσματα στο εσωτερικό επιθήλιο της ουροδόχου κύστεως, που είναι γνωστό και ως ουροθήλιο 47 αλλά και σε λοιπά όργανα του ουροποιητικού συστήματος. Ορισμένοι ωστόσο συγγραφείς υποστηρίζουν πως η KIUT μπορεί να παρατηρηθεί και σε υπο-αναισθητικές δόσεις κεταμίνης (0,5-1,0 mg/kg).…”